Behavioral and health outcomes from the NRG Oncology/NSABP B-36 trial comparing two different adjuvant therapy regimens for early-stage node-negative breast cancer

Breast Cancer Research and Treatment - The NSABP B-36 compared four cycles of doxorubicin and cyclophosphamide (AC) with six cycles of 5-fluorouracil, epirubicin, and cyclophosphamide (FEC-100) in...     

On comparing methods for discriminating between actually negative and actually positive subjects with FROC type data

The task of searching and detecting multiple abnormalities depicted on an image, or a series of images, is a common problem in different areas such as military target detection or diagnostic medical imaging. A free response receiver operating characteristic (FROC) approach for assessing performance in many of these scenarios entails marking the locations of suspected abnormalities and indicating a level of suspicion at each of the marked locations. One of the important characteristics of a system being evaluated under the FROC paradigm is its performance in the conventional ROC domain, namely classifying a subject (or a unit of interest) as "negative" or "positive" in regard to the presence of the abnormality (or any of the abnormalities) of interest. With FROC data we can compare subjects by specifying a function of multiple scores within a subject. This approach allows formulating subject-based ROC type indices that can be estimated using existing ROC concepts. In this article we focus on indices that reflect the ability of the system to discriminate between actually negative and actually positive subjects. We consider a previously proposed index that is based on the comparison of the highest scores on subjects and two new indices that are based on potentially more stable comparison functions, namely comparison of average scores and stochastic dominance. Based on these indices we develop nonparametric procedures for comparing subject-based discriminative ability of diagnostic systems being evaluated under the FROC paradigm. We also investigate the properties of the statistical procedures in a simulation study.     

Pathobiology of small invasive breast cancers without metastases (T1a/b, N0, M0): National Surgical Adjuvant Breast and Bowel Project (NSABP) protocol B-21

BACKGROUND: Uncertainties continue to exist concerning the outcomes and management of small (T1a/b N0 M0) invasive breast cancers. METHODS: A central pathology review was performed of 638 such lesions from National Surgical Adjuvant Breast and Bowel Project (NSABP) clinical trial B-21. RESULTS: Univariate analysis revealed a high risk for ipsilateral breast tumor recurrence with tumors exhibiting a ductal carcinoma in situ component or poor nuclear grade. The converse (protective effect) was found with tumors arising in radial scars, those of tubular histologic type, and those with moderate/marked tumor stroma. The correlations were generally similar for disease-free survival. However, only nuclear grade was found to be independently significant for both of these outcomes. Only lymphatic tumor extension was univariately and multivariately significant for overall survival. CONCLUSIONS: The long-term results of follow-up (median, 11.2 years) from the current trial continue to support the need for local breast irradiation and adjuvant therapy in the management of patients with these small cancers.     

Prospective trial comparing full-field digital mammography (FFDM) versus combined FFDM and tomosynthesis in a population-based screening programme using independent double reading with arbitration

Objectives

To compare double readings when interpreting full field digital mammography (2D) and tomosynthesis (3D) during mammographic screening.

Methods

A prospective, Ethical Committee approved screening study is underway. During the first year 12,621 consenting women underwent both 2D and 3D imaging. Each examination was independently interpreted by four radiologists under four reading modes: Arm A—2D; Arm B—2D?+?CAD; Arm C—2D?+?3D; Arm D—synthesised 2D?+?3D. Examinations with a positive score by at least one reader were discussed at an arbitration meeting before a final management decision. Paired double reading of 2D (Arm A?+?B) and 2D?+?3D (Arm C?+?D) were analysed. Performance measures were compared using generalised linear mixed models, accounting for inter-reader performance heterogeneity (P?<?0.05).

Results

Pre-arbitration false-positive scores were 10.3 % (1,286/12,501) and 8.5 % (1,057/12,501) for 2D and 2D?+?3D, respectively (P?<?0.001). Recall rates were 2.9 % (365/12,621) and 3.7 % (463/12,621), respectively (P?=?0.005). Cancer detection was 7.1 (90/12,621) and 9.4 (119/12,621) per 1,000 examinations, respectively (30 % increase, P?<?0.001); positive predictive values (detected cancer patients per 100 recalls) were 24.7 % and 25.5 %, respectively (P?=?0.97). Using 2D?+?3D, double-reading radiologists detected 27 additional invasive cancers (P?<?0.001).

Conclusion

Double reading of 2D?+?3D significantly improves the cancer detection rate in mammography screening.

Key Points

? Tomosynthesis-based screening was successfully implemented in a large prospective screening trial. ? Double reading of tomosynthesis-based examinations significantly reduced false-positive interpretations. ? Double reading of tomosynthesis significantly increased the detection of invasive cancers.     

Performance of breast cancer screening using digital breast tomosynthesis: results from the prospective population-based Oslo Tomosynthesis Screening Trial

Purpose

Digital breast tomosynthesis (DBT) has the potential to overcome limitations of conventional mammography. This study investigated the effects of addition of DBT on interval and detected cancers in population-based screening.

Methods

Oslo Tomosynthesis Screening Trial (OTST) was a prospective, independent double-reading trial inviting women 50–69 years biennially, comparing full-field digital mammography (FFDM) plus DBT with FFDM alone. Performance indicators and characteristics of screen-detected and interval cancers were compared with two previous FFDM rounds.

Results

24,301 consenting women underwent FFDM + DBT screening over a 2-year period. Results were compared with 59,877 FFDM examinations during prior rounds. Addition of DBT resulted in a non-significant increase in sensitivity (76.2%, 378/496, vs. 80.8%, 227/281, p = 0.151) and a significant increase in specificity (96.4%, 57229/59381 vs. 97.5%, 23427/24020, p < .001). Number of recalls per screen-detected cancer decreased from 6.7 (2530/378) to 3.6 (820/227) with DBT (p < .001). Cancer detection per 1000 women screened increased (6.3, 378/59877, vs. 9.3, 227/24301, p < .001). Interval cancer rate per 1000 screens for FFDM + DBT remained similar to previous FFDM rounds (2.1, 51/24301 vs. 2.0, 118/59877, p = 0.734). Interval cancers post-DBT were comparable to prior rounds but significantly different in size, grade, and node status from cancers detected only using DBT. 39.6% (19/48) of interval cancers had positive nodes compared with only 3.9% (2/51) of additional DBT-only-detected cancers.

Conclusions

DBT-supplemented screening resulted in significant increases in screen-detected cancers and specificity. However, no significant change was observed in the rate, size, node status, or grade of interval cancers.ClinicalTrials.gov: NCT01248546.

     

Binary and multi-category ratings in a laboratory observer performance study: a comparison

The authors investigated radiologists, performances during retrospective interpretation of screening mammograms when using a binary decision whether to recall a woman for additional procedures or not and compared it with their receiver operating characteristic (ROC) type performance curves using a semi-continuous rating scale. Under an Institutional Review Board approved protocol nine experienced radiologists independently rated an enriched set of 155 examinations that they had not personally read in the clinic, mixed with other enriched sets of examinations that they had individually read in the clinic, using both a screening BI-RADS rating scale (recall/not recall) and a semi-continuous ROC type rating scale (0 to 100). The vertical distance, namely the difference in sensitivity levels at the same specificity levels, between the empirical ROC curve and the binary operating point were computed for each reader. The vertical distance averaged over all readers was used to assess the proximity of the performance levels under the binary and ROC-type rating scale. There does not appear to be any systematic tendency of the readers towards a better performance when using either of the two rating approaches, namely four readers performed better using the semi-continuous rating scale, four readers performed better with the binary scale, and one reader had the point exactly on the empirical ROC curve. Only one of the nine readers had a binary "operating point" that was statistically distant from the same reader's empirical ROC curve. Reader-specific differences ranged from -0.046 to 0.128 with an average width of the corresponding 95% confidence intervals of 0.2 and p-values ranging for individual readers from 0.050 to 0.966. On average, radiologists performed similarly when using the two rating scales in that the average distance between the run in individual reader's binary operating point and their ROC curve was close to zero. The 95% confidence interval for the fixed-reader average (0.016) was (-0.0206, 0.0631) (two-sided p-value 0.35). In conclusion the authors found that in retrospective observer performance studies the use of a binary response or a semi-continuous rating scale led to consistent results in terms of performance as measured by sensitivity-specificity operating points.